Serum hepcidin as a host-derived biomarker of disease severity and risk stratification in tuberculosis

Hepcidin is a key regulator of systemic iron metabolism. Hepcidin may reflect the inflammatory activity and disease burden in tuberculosis. However, prospective evidence on the prognostic value of serum hepcidin and other host-biomarkers in tuberculosis is limited. We evaluated the association of hepcidin with disease severity and outcomes.

This prospective cohort study enrolled consecutive adults (age ≥ 18 years) with newly diagnosed tuberculosis. Baseline serum hepcidin, adenosine deaminase (ADA), and creatine kinase-MB (CK-MB) levels were measured. Disease severity was assessed using a predefined tuberculosis severity score. The prognostic performance of biomarkers was evaluated using receiver operating characteristic analysis and multivariable logistic regression.

Among 140 patients (median age, 48 years; 67.1% male), 25% had pulmonary tuberculosis, 25% extrapulmonary tuberculosis, and 50% disseminated disease; HIV co-infection was present in 16.4%. The 3-month all-cause mortality rate was 22.1%. Serum hepcidin levels were significantly higher in severe than non-severe tuberculosis (201.5 vs. 145.9 ng/mL; p = 0.017), but were not associated with 3-month mortality. Conversely, CK-MB was significantly elevated among non-survivors (24.5 vs. 13.8 U/L; p < 0.001). CK-MB showed good predictive performance for mortality (AUC 0.795), while ADA demonstrated moderate discrimination (AUC 0.647). The ADA/CK-MB combination showed the highest discriminative performance for mortality prediction (AUC 0.82). Triple-marker panel (Hepcidin + ADA+CK-MB) provided the best discrimination for severe disease (AUC 0.717).

Serum hepcidin was associated with disease severity in tuberculosis but was not associated with 3-month mortality. Combined biomarker models showed promising prognostic performance, warranting further validation in larger multicentre studies.